The objectives of the proposed research are to understand the pathogenesis of diffuse glomerular disease in man (i.e., glomerulonephritis and nephrotic syndrome) through an investigation of: the nature and role of the glomerular mesangium in renal disease; the effects of immunologic, biochemical and irradiation injury on mesangial function; the factors that influence glomerular mesangial uptake and clearance of macromolecules; and the relationship of mesangial function to increased glomerular capillary permeability to protein. The methods employed will include renal transplanation, and renal perfusion in rats and quantitative determination of glomerular mesangial content of macromolecules, biochemical, radioisotope, histologic, immunopathologic and immunologic techniques.